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Analysis of 2,3,7,8-tetrachlorodibenzo-p-dioxin responsive DNA sequences upstream of the cytochrome P sub 1 -450 gene

Thesis/Dissertation ·
OSTI ID:7243151
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD, dioxin) increases transcription of the cytochrome P{sub 1}-450 gene in a mouse hepatoma cell line. An intracellular TCDD receptor protein (the Ah receptor), and a cisacting enhancer element upstream of the cytochrome P{sub 1}-450 gene are required for TCDD-dependent transcription. In a clonal cell line stably transfected with a single copy of a plasmid containing the enhancer upstream of a viral promoter and the chloramphenicol acetyltransferase (CAT) gene, TCDD induces CAT transcription at the appropriate start site. Induction displays inducer specificity, TCDD sensitivity, and a time course of induction similar to those of the endogenous cytochrome P{sub 1}-450 gene. I conclude that the enhancer element and the receptor represent a general mechanism through which TCDD can mediate its pleiotropic effects.
Research Organization:
Stanford Univ., CA (USA)
OSTI ID:
7243151
Country of Publication:
United States
Language:
English